Abstract
Arylalkylamine N-acetyltransferase (AANAT) or Serotonin N-acetyltransferase is one of the key enzymes for the synthesis of melatonin in humans. In the process, the regular binding partner of this AANAT protein is 14-3-3 protein. A mutation of A129T in the AANAT protein leads to decreased functionality of the AANAT protein. So far the mechanistic details of this loss of binding have not been elucidated. In the present work, we tried to utilize structural bioinformatic approach to understand the differences in pattern of bindings between AANAT wild type and mutant forms. We used molecular mechanics calculations to describe the interactions of wild type and mutant AANAT proteins with its binding partner 14-3-3 proteins. So far, this is the first report that characterizes the difference in binding between the two forms of the protein. Therefore, the results from this study may be useful for the development of drugs in patients having impaired melatonin synthesis.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bagchi, A., Mortb, M., Lic, B., Xind, F., Carlisec, C., Oronc, T., Powellc, C., Youne, E., Radivojacd, P., Cooperb, D.N., Mooneyc, S.D.: Analysis of features from protein-protein hetero-complex structures to predict protein interaction interfaces using machine learning: CIMTA. Procedia Technol. 10, 62–66 (2013)
Ganguly, S., Weller, J.L., Ho, A., Chemineau, P., Malpaux, B., Klein, D.C.: Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc. Natl. Acad. Sci. USA 102(4), 1222–1227 (2005)
Hickman, A.B., Klein, D.C., Dyda, F.: Melatonin biosynthesis: the structure of serotonin N-acetyltransferase at 2.5 Å resolution suggests a catalytic mechanism. Mol. Cell 1, 23–32 (1999)
Blomeke, B., Golka, K., Griefahn, B., Roemer, H.C.: Arylalkylamine N-acetyltransferase (AANAT) genotype as a personal trait in melatonin synthesis. J. Toxicol Environ. Health A 71(13–14), 874–876 (2008)
Bijlenga, D., Van Someren, E.J., Gruber, R., Bron, T.I., Kruithof, I.F., Spanbroek, E.C., Kooij, J.J.: Body temperature, activity and melatonin profiles in adults with attention-deficit/hyperactivity disorder and delayed sleep: a case-control study. J. Sleep Res. 6, 607–616 (2013)
Fu, H., Subramanian, R.R., Masters, S.C.: 14-3-3 PROTEINS: structure, function, and regulation. Ann. Rev. Pharmacol. Toxicol. 40, 617–647 (2000)
Wolf, E., De Angelis, J., Khalil, E.M., Cole, P.A., Burley, S.K.: X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition. J. Mol. Biol. 317(2), 215–224 (2002)
Choong, Y.S., Tye, G.J., Lim, T.S.: Minireview: applied structural bioinformatics in proteomics. Protein J. 32, 505–511 (2013)
Cukuroglu, E., Engin, E.H., Gursoy, A., Keskin, O.: Hot spots in protein-protein interfaces: towards drug discovery. Prog. Biophys. Mol. Biol., 1–9 (2014)
Rao, S.V., Srinivas, K., Sujini, G.N., Sunand Kumar, G.N.: Protein-protein interaction detection: methods and analysis. Int. J. Proteomics 2014, Article ID 147648 (2014)
Sudha, G., Nussinov, R., Srinivasan, N.: An overview of recent advances in structural bioinformatics of protein-protein interactions and a guide to their principles. Prog. Biophys. Mol. Biol. 116(2), 141–150 (2014)
Acknowledgment
The authors would like to thank the DST-PURSE program 2012-2015 going on in the Department of Biochemistry and Biophysics, University of Kalyani for providing different instrumental and infrastructural support. The authors are also thankful to the DBT sponsored Bioinformatics Infrastructure Facility in the Department of Bio-chemistry and Biophysics, University of Kalyani for the necessary support.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer India
About this paper
Cite this paper
Ali, A., Bhattacharjee, S., Bagchi, A. (2015). Structural Analyses of the Mode of Binding Between AANAT Protein with 14-3-3 Protein Involved in Human Melatonin Synthesis. In: Mandal, J., Satapathy, S., Kumar Sanyal, M., Sarkar, P., Mukhopadhyay, A. (eds) Information Systems Design and Intelligent Applications. Advances in Intelligent Systems and Computing, vol 340. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2247-7_14
Download citation
DOI: https://doi.org/10.1007/978-81-322-2247-7_14
Published:
Publisher Name: Springer, New Delhi
Print ISBN: 978-81-322-2246-0
Online ISBN: 978-81-322-2247-7
eBook Packages: EngineeringEngineering (R0)